Translational research : the journal of laboratory and clinical medicine
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The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. ⋯ Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.
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Review
Pericyte-endothelial crosstalk: implications and opportunities for advanced cellular therapies.
Pericytes are mural cells of the microcirculation that have been shown to play key roles in regulating microvascular morphogenesis and stability throughout each tissue bed and organ system assessed. Of note, recent work has revealed that pericytes share several characteristics with mesenchymal- and adipose-derived stem cells, suggesting there may be lineage-related connections among bona fide pericytes and these vascular "progenitors," which can assume a perivascular position in association with endothelial cells. ⋯ Crucial to the development of such therapies is a comprehensive understanding of the origin and fate regulating these related cell types as well as the unveiling of the molecular mechanisms by which pericytes and endothelial cells communicate. Such mechanistic inputs, which disrupt normal cellular crosstalk during disease inception and progression, offer opportunities for intervention and are discussed in the context of the vasculopathies accompanying tumor growth, diabetes, and fibrosis.
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The diabetes pandemic incurs extraordinary public health and financial costs that are projected to expand for the foreseeable future. Consequently, the development of definitive therapies for diabetes is a priority. Currently, a wide spectrum of therapeutic strategies-from implantable insulin delivery devices to transplantation-based cell replacement therapy, to β-cell regeneration-focus on replacing the lost insulin-producing capacity of individuals with diabetes. ⋯ Second, the presence of pancreatic facultative endocrine progenitor cells has been established. Third, the malleability of cellular identity has availed the possibility of generating β cells from other differentiated cell types. Here, we review the exciting developments surrounding endogenous sources of β-cell production and consider the potential of realizing a regenerative therapy for diabetes from adult tissues.